TY - JOUR
T1 - Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription
AU - Kilpinen, Helena
AU - Waszak, Sebastian M.
AU - Gschwind, Andreas R.
AU - Raghav, Sunil K.
AU - Witwicki, Robert M.
AU - Orioli, Andrea
AU - Migliavacca, Eugenia
AU - Wiederkehr, Michaël
AU - Gutierrez-Arcelus, Maria
AU - Panousis, Nikolaos I.
AU - Yurovsky, Alisa
AU - Lappalainen, Tuuli
AU - Romano-Palumbo, Luciana
AU - Planchon, Alexandra
AU - Bielser, Deborah
AU - Bryois, Julien
AU - Padioleau, Ismael
AU - Udin, Gilles
AU - Thurnheer, Sarah
AU - Hacker, David
AU - Core, Leighton J.
AU - Lis, John T.
AU - Hernandez, Nouria
AU - Reymond, Alexandre
AU - Deplancke, Bart
AU - Dermitzakis, Emmanouil T.
PY - 2013
Y1 - 2013
N2 - DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.
AB - DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.
UR - https://www.scopus.com/pages/publications/84887320563
U2 - 10.1126/science.1242463
DO - 10.1126/science.1242463
M3 - Article
SN - 0036-8075
VL - 342
SP - 744
EP - 747
JO - Science
JF - Science
IS - 6159
ER -